Methylenedioxy-phenoxy derivatives as agents for upsetting hormone balance in insects

ABSTRACT

Methylenedioxy substituted benzyloxy or phenyloxy ethers of aliphatic hydrocarbons, wherein the aliphatic group contains between 6 and 11 carbon atoms. These ethers are useful in killing and preventing the proliferation of insects by upsetting their hormonal balance.

Elite States Patent [191 Chodnekar et al.

[ Aug. 13, 1974 [73] Assignee: Hoffman-La Roche Inc., Nutley,

[22] Filed: Apr. 24, 1972 [21] Appl. No.: 247,083

Related US Application Data [62] Division of Ser. No. l23,l05, March 10, 1971, Pat.

[30] Foreign Application Priority Data Mar. 25, 1970 Switzerland 4620/70 [52] US. Cl 424/278, 424/DIG. 12, 424/282, 260/3405 [51] Int. Cl A0ln 9/28 [58] Field of Search 424/282, DIG. i2, 278

[56] References Cited UNITED STATES PATENTS 3,563,982 2/l97l I Bowers 260/3405 3,637,752 H1972 Siddall 424/282 OTHER PUBLICATIONS Borkovec, A., Insect Chemosterilants, Vol. V]! (1966), PP. 61-63.

Bowers, Science, Vol. 164 (3877), 1969, pp. 323-325.

Primary Examiner-Vincent D. Turner Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe; William H. Epstein [57] ABSTRACT Methylenedioxy substituted benzyloxy or phenyloxy ethers of aliphatic hydrocarbons, wherein the aliphatic group contains between 6 and l 1 carbon atoms. These ethers are useful in killing and preventing the proliferation of insects by upsetting'their hormonal balance.

4 Claims, No Drawings METHYLENEDIOXY-PHENOXY DERIVATIVES AS AGENTS FOR UPSETTING HORMONE BALANCE IN INSECTS This is a division, of application Ser. No. 123,105 filed Mar. 10, 1971 entitled Methylenedioxy-Phenoxy Derivatives now U.S. Pat. No. 3,686,222.

SUMMARY OF THE INVENTION In accordance with this invention, it has been found that compounds of the formula:

wherein R and R are methyl or ethyl, R is hydrogen or methyl, A and B individually are hydrogen or A and B taken together are a carbon to carbon bond or an oxygen bridge, X is oxygen or OCH and n is an integer of from O to l; upset the hormone balance of pests such as insects to prevent them from growing and reproducing.

The compounds of formula I are prepared by reacting a compound of the formula:

wherein R,, R R A, B and n are as above and Y is a halogen; with a compound of the formula:

DETAILED DESCRIPTION OF THE INVENTION As used throughout this application, the term halogen or halo, when not expressly stated otherwise, includes all four halogens, i.e., fluorine, chlorine, bromine and iodine. As also used herein, the term alkali metal includes the metals of the first main group of the periodic chart, e.g., lithium, sodium and potassium.

II I

The compounds of formula I are suitable for combatting pests. In contrast to most of the known pesticides which kill, cripple or drive away the pests, such as contact-poisons and feed-poisons, the compounds of formula I interfere with the hormonal system of the pest organism. In insects, for example, the transformation to the imago, the laying of viable eggs and the development of laid normal eggs is disturbed. The sequence of generations is interrupted and the animals are indirectly killed. The-compounds of formula I are also B l AMH l AIR-s X practically non-poisonous to vertebrate animals, the toxicity of these compounds being over 1,000 mg/kg body weight. Furthermore, these new compounds are readily degraded. The risk of accumulation is therefore excluded. Therefore, these compounds can be unhesitatingly employed for combatting pests in animals, plants and provisions.

The compounds of formula I are especially suitable for combatting invertebrate animals such as arthropods and nematodes. These compounds are especially useful against insects such as Tenebrio molitor (yellow meal worm), flies, potato beetles, Prodenia, Dysdercus, Ephestia kuhniella (flour moth), aphids or spider-mites. In general, applying a concentration of the compound of formula I as the active substance of from about 10' to IO' g/cm of the material to be protected, i.e., foodstuffs, feeds, textiles, plants etc., suffices to ensure the desired effect.

Generally, it is preferred to utilize the active substance in a composition with a suitable inert carrier. Any conventional inert carrier can be used.

The compounds'of formula I can, for example, be employed in the form of emulsions, suspensions, dusting agents, solutions or aerosols. Such pesticides contain the compound of formula I in concentrations of from about 0.01 percent to about 0.5 percent and preferably about 0.1 percent. In particular cases, the goods which are to be protected (e.g., foodstuffs, seeds, textiles) can also be directly impregnated with the active substance concerned or with a solution of the active substance. The active substance can furthermore also be. applied in a form which releases the active substance only by the action of external influences (e.g., in contact with moisture) or only in the animal body itself.

The compounds of formulal above can be used as solutions suitable for spraying on the material to be protected, which solutions can be prepared by dissolving or dispersing these compounds in a solvent such as mineral oil fractions; cold tar oils; oils of vegetable or animal origins; hydrocarbons such as napthalenes; ketones such as methyl ethyl ketone; or chlorinated hydrocarbons such as tetrachloroethylene, tetrachlorobenzene, and the like. The compounds of formula I above can also be prepared in forms suitable for dilution with water to form aqueous liquids such as, for example, emulsion concentrates, pastes or powders. The compounds of formula I above can be combined with solid carriers for making, dusting or strewing powders, for example, talc, kaolin, bentonite, calcium carbonate, calcium phosphate, etc. The compositions containing the compounds of formula I above can contain, if desired, emulsifiers, dispersing agents, wetting agents, or other active substances such as fungicides, bacteriacides, nematocides, fertilizers and the like. The materials which are to be protected act as bait for the insect. In this manner, the insect, by contacting the material impregnated with a compound of formula I above, also contacts the compound itself.

In accordance with this invention, the preferred compounds of formula I are as follows: the compounds of the formula:

wherein A and B are as above; especially: 2-methyl-6-[(3,4-methylenedioxy)-benzyloxyl-heptane;

the compounds of the formula:

wherein A and B are as above; especially:

3-methyl-7-[(3,4-methylenedioxy)-phenoxy]-oct- 3-ene;

6-methyl- 2-[ 3 ,4-methylenedioxy)-phenoxy octane; and

5,6-epoxy-6-methyl-2-[(3,4-methyleneclioxy)- phenoxy1-octane; the compounds of the formula:

wherein A and B are as above; especially:

2,3-dimethyl-6-[ 3 ,4-methylenedioxy )-phenoxy hept-2-ene;

2,3-epoxy-2,3-dimethyl-6- 3 ,4-methylenedioxy phenoxy1-heptane; and v 2,3-dimethyl-6-[(3,4-methylenedioxy)-phenoxy]- heptane; the compounds of the formula:

wherein A and B are as above; the compounds of the formula:

wherein A and B are as above; the compounds of the formula:

wherein A and B are as above; especially:

4-methyll t 3 ,4-methylenedioxy )-phenox l-hex- 3-ene;

4-methyll 3,4-methylenedioxy)-phenoxy]- hexane; and

3 ,4-epoxy-4-methyll 3 ,4-methylenedioxy)- phenoxy1-hexane; the compounds of the formula:

wherein A and B are as above; the compounds of the formula:

the compounds of the formula:

wherein 3, Aand'fi'fi'gggggg especially:

'l 3 ethylenedioxy )-phenoxy nonane;

3-Methyl-7-ethyl- 3 ,4-methylenedioxy )-phenoxy oct-3-ene;

6,7-Epoxy-7-methyl-3-[(3,4-methylenedioxy)- phenoxy1-nonane; and

6,7-Epoxy-6,7-dimethyl-3-[(3,4-methylenedi0xy) phenoxy]-nonane.

The compounds of formula I are expediently obtained by reacting a halide of formula II with an alkali metal salt of formula III. The compounds of formula ll and III are known compounds which are reacted together in a well known manner to form the compounds of formula I. In preparing the compounds of formula I, the alkali metal salt of formula 111, formed in situ is first suspended in an inert organic solvent, and then, the halide of formula ll is added thereto. Any of the halides of the compounds of formula ll can be used to form the compound of formula I with the chlorides and bromides being the preferred halides. In carrying out this reaction, any conventional inert organic solvent can be used.

The alkali metal salt of formula Ill can be suitably obtained by the reaction between a corresponding phenol or benzyl alcohol and an alkali metal base. Although any alkali metal base can be used, the alkali metal hydrides, alkali metal alkanolates and the alkali metal hydroxides are the preferred bases and sodium is the corresponding, preferred alkali metal.

The formation of the alkali metal salt of formula III is suitably carried out in the presence of an inert organic solvent. This reaction can be conveniently carried out in the same inert organic solvent used in the reaction between the compounds of formulas II and Ill. Although the selection of the inert organic solvent for these reactions is not critical, when an alkali metal hydride is used to prepare the compound of formula III, the preferred solvents are dioxane, tetrahydrofuran, dimethylformamide, and diethyl ether; when an alkali metal alkanolate is used, the preferred solvents are the corresponding alkanols (e.g. sodium methylate in methanol) and when an alkali metal hydroxide is used, the preferred solvents are the alkanols, particularly ethanol and methanol.

Another means of reacting the halide of formula II with the alkali metal salt of formula III, to form the compound of formula I, is by carrying out this reaction in the presence of a phenol and an alkali metal carbonate. In carrying out this reaction, any conventional inert solvent can be utilized, with acetone being the preferred solvent. Also, in carrying out this reaction, any alkali metal carbonate can be used, potassium carbonate being the preferred carbonate.

In carrying out the above reactions between the compounds of formula II and III, temperature and pressure are not critical, and the reactions can be suitably conducted in a temperature range lying between 0C. and the boiling temperature of the reaction mixture. Preferably, the reactions are also conducted in the presence of an aprotonic solvent such as hexamethyl phosphoric acid triamide. The reaction mixture can then be worked up in a conventional manner by being heated under reflux, cooled, poured onto ice and extracted with diethyl ether. The ether extract can then be washed with water, dried and evaporated. The residual compound of formula I can then be further purified by distillation or adsorption, preferably on Kieselgel or aluminum oxide.

The compounds of formula I wherein A and B taken together are a carbon to carbon bond can, if desired, be hydrogenated or epoxidized in a manner known per The hydrogenation of unsaturated compounds of formula I can be carried .out by conventional hydrogenation means such as by hydrogenating in the presence of a conventional hydrogenation catalyst. In carrying out this reaction, temperature and pressure are not critical, a temperature range between about 25C. and the boiling temperature of the solvent used and atmospheric or elevated pressures being preferred. Suitable as hydrogenation catalyst are, for example, Raney-nickel or preferably the noble metals, with palladium and platinum being especially preferred. Suitable as solvents are acetic acid ethyl ester and alkanols such as methanol and ethanol.

formula:

I 0 R1 R Br I /l\l o orr in n Y H v wherein R R R n and X are as above. In this reaction, temperature and pressure are not critical, the reaction being preferably carried out between 0C. and

25C. In carrying out this reaction, the unsaturated compound of formula I is preferably initially suspended in water. Then an inert organic solvent is added to the suspension'to give a homogeneous concentrated solution of the compound of formula I in water and organic solvent. Any conventional inert organic solvent can be The compounds of formula I wherein A and B taken together are a carbon to carbon bond can be converted into a compound of formula I wherein A and B taken together are an oxygen bridge by any conventional epoxidation technique. The epoxidation of unsaturated compounds of formula I can be expediently carried out by treating the compound of formula I with an organic peracid. This reaction is carried out by first dissolving the compounds in an inert solvent. In carrying out this reaction, any inert organic solvent can be used, the halogenated hydrocarbons being preferred with methyutilized in this reaction, dioxane, tetrahydrofuran and 1 ,Z-dimethoxyethane being preferred. N- bromosuccinimide is then introduced portionwise into this homogeneous solution to yield the bromohydrin of formula IV.

These bromohydrins can then be converted by the action of a base to the corresponding epoxide. In carrying out this reaction, any conventional base is suitable, with the alkali metal alkanolates being preferred, especially sodium methylate in methanol. In this reaction, temperature and pressure are not critical, the reaction being preferably carried out between 0C. and 25C. Any conventional inert organic solvent can be utilized in this reaction, dioxane tetrahydrofuran and 1,2- dimethoxymethane being preferred.

In the species of the compounds of formula I wherein the side-chain is unsaturated or epoxidized, these species exist as a cis/trans isomer mixture. The isomer mixture can be separated in a conventional manner by, for example, fractional distillation or gas chromatography. The halides of formula II, wherein the chain, is epoxidized or unsaturated can exist as a mixture of cis and trans isomers. This isomeric mixture can, if desired, be

separated into the all cis and all trans isomers in a conventional manner by, for example, fractional distillation.

The following examples illustrate the invention. All temperatures are stated in degrees centigrade.

EXAMPLE I 4.8 g of a 50 percent by weight suspension of sodium hydride in mineral oil was washed twice with hexane in an inert gas atmosphere, then added to 40 ml of absolute tetrahydrofuran. With ice-cooling and stirring, a solution of 13.8 g of 3,4-methylenedioxy-phenol in ml of absolute tetrahydrofuran was addeddropwise to the sodium hydride-tetrahydrofuran mixture. The resulting mixture was further stirred at room temperature for I hour. Subsequently' 23 g of 2-bromo-6-methylphenoxy]-hept-2-ene was purified by adsorption on Kieselgel with hexane and diethyl ether (4:1 partsby volume). B.P. 9799C/0.04 mmHg; m, 1.5200.

EXAMPLE 2 By utilizing the procedure of Example 1, 2-bromo-6- methyl-oct-S-ene and 3,4-methylenedioxy-phenol were converted into 3-methyl-7-[ 3 ,4-methylenedioxy phenoxy]-oct-3-ene. B.P. 108-110C/0.1 mml-lg; n 1.5182.

EXAMPLE 3 By utilizing the procedure of Example 1, l-bromo-4- methyl-hex-3-ene and 3,4-methylenedioxy-phenol were converted into 4-methyl-l -[(3 ,4- methylenedioxy)-phenoxyl-hex-3-ene. B P. 90C/0.001 mml-lg (bulb-tube distillation); n,, 1.5286.

EXAMPLE 4 I By utilizing the procedure of Example 1, l-bromo- 3,4-epoxy-4-methyl-hexane and 3,4-methylenedioxyphenol were converted into 3,4-epoxy-4-methyl-[(3,4- methylenedioxy)-phenoxy]-hexane. B.P. 100C/0.001 mmHg (bulb-tube distillation); n 1.5222.

EXAMPLE 5 9.4 g of a 50 percent by weight suspension of sodium hydride in mineral oil was washed twice with hexane in an inert gas atmosphere, and then added to 100 ml of absolute dimethylformamide. With ice-cooling and stirring, a solution of 30 g of piperonyl alcohol in 100 ml of absolute dimethylformamide was added dropwise to the sodium hydride-dimethylformamide mixture. The resulting mixture was further stirred at room temperature for 1 hour. 40 g of 2-bromo-6-methyl-heptane was subsequently added dropwise. Then, the reaction mixture was heated to 70C. for 2 hours, then cooled, poured onto ice-water and exhaustively extracted with diethyl ether. The ether extract was washed with saturated, aqueous sodium chloride solution dried over sodium sulphate and evaporated under reduced pressure. The residual oily 2-methyl-6-[(3,4-methylenedioxy)- benzyloxy]-heptane was purified by adsorption on Kieselgel with hexane and diethyl ether (4:1 parts by volume). B.P. 170-172C/1 mmHg.

EXAMPLE 6 3.1 g of 2-methyl-6-[(3,4-methylenedioxy)-phenoxy]-hept-2- ene was dissolved in 100 ml of acetic acid ethyl ester and hydrogenated at room temperature of about 25C. and 1 atmosphere pressure in the presence of 0.5 g of platinum oxide. The hydrogenation was terminated after the uptake of 1 mol-equivalent of hydrogen. The catalyst was filtered off and the clear solution evaporated under reduced pressure. The residual 2- methyl-6-[ 3 ,4-methylenedioxy)-phenoxy ]-heptane was distilled in the bulb-tube. B.P. lOOC/0.001 mmHg; n 1.5004.

EXAMPLE 7 By utilizing the procedure of Example 6, 3-methyl-7- [(3,4-methylenedioxy)-phenoxy]-oct-3-ene was con verted into 6-methyl-2-[ 3 ,4-methylenedioxy phenoxy]-octane. B.P. 104105C/0.09 mml-lg; n 1.4994.

EXAMPLE 8 By utilizing the procedure of Example 6, 4-methyl-1- [(3,4-methylenedioxy)-phenoxy]-hex-3-ene was converted into 4-methyl- 1 3 ,4-methylenedioxy)- phenoxyl-hexane. B.P.'100C/0.00l mml-lg (bulb-tube distillation); r1 1.5057.

EXAMPLE 9 By utilizing the procedure of Example 6, 2,3- dimethyl-6-[ 3 ,4-methylenedioxy )-phenoxy -hept- 2-ene was converted into 2,3-dimethyl-6-[(3,4- methylenedioxy)-phenoxy]-heptane. B.P. ca 120C/.0O1 mmHg (bulb-tube distillation); n 1.4994.

EXAMPLE 10 6.2 g of 2-methyl-6-[(3,4-methylenedioxy)- phenoxy]-hept-2-ene was dissolved in 100 ml of methylene chloride. With ice-cooling and stirring, 5.4 g of percent by weight m-chloroperbenzoic acid was added portionwise and the resulting mixture was further stirred for 2 hours. The reaction mixture was then diluted with mlof methylene chloride and successively washed with ice-cold l-N caustic soda and saturated, aqueous sodium chloride solution. The organic phase was separated off, dried over sodium sulphate and evaporated under reduced pressure. The residual 2,3-epoxy-2-methyl-6- 3 ,4-methylenedioxy phenoxy]-heptane was purified by adsorption on Kieselgel with hexane and diethyl ether (4:1 parts by volume). B.P. C/0.001 mml-lg (bulb-tube distillation); n 1.5142.

EXAMPLE 1 1 By utilizing the'procedure of Example 10, 3-Methyl- 7 3 ,4-methylenedioxy )-phenoxy]-oct-3-ene was converted into 5,6-epoxy-6-methyl-2-[(3,4- methylenedioxy)-phenoxy]-octane. B.P. 120C/0.00l mmHg (bulb-tube distillation); n 1.5120.

EXAMPLE 12 By utilizing the procedure of Example 10, 4-methyl- 1-[(3,4-methylenedioxy)-phenoxy]-hex-3-ene was converted into 3 ,4-epoxy-4-methyl- 1 3 ,4- methylenedioxy)-phenoxy]-hexane. B.P. 100C/0.001 mmHg (bulb-tube distillation); n 1.5222.

EXAMPLE 13 By utilizing the procedure of Example 10, 2,3- dimethyl-6-[(3,4-methylenedioxy)-phenoxy]-hept- 2-ene was converted into 2,3-epoxy-2,3-dimethyl-6- [(3,4-methylenedioxy)-phenoxy]-heptane. B.P. ca C/.001 mmHg (bulb-tube distillation); u 1.5118.

. EXAMPLE 14 To a solution of 13.8 g 3,4-en obtained. in 100 ml of anhydrous acetone were successively added 20.7 g potassium carbonate and 23.6 g 2-bromo-5,6-dimethylhept-S-ene, and the reaction mixture was heated and stirred for 96 hours under reflux. Subsequently, the reaction mixture was evaporated, poured onto water and extracted with diethyl ether. The ether extract was then washed with .l-N sodium hydroxide and saturated, aqueous sodium chloride solution, dried over sodium sulfate and evaporated. Through distillation under high vacuum was pure 2,3 -dimethyl-6-[ 3 ,4- methylenedioxy)-phenoxy]-hept-2-enobtained. B.P.

The tests described in the following Examples were carried out with the following preferred active substances as representative examples of the utility of the methylenedioxy-phenyl derivatives of the instant invention:

A. 2,3-epoxy-2-methyl-6-[ 3 ,4-methylenedioxy phenoxy]-heptane B. 3-methyl-7-[ 3 ,4-methy1enedioxy )-phenoxy l-oct- 3-ene;

C. ,6-epoxy-6-methyl-2-[( 3 ,4-methylenedioxy EXAMPLE 15 A filter paper strip [90 cm was sprayed with an acetonic solution of an active substance of this invention. An untreated paper strip and a paper strip soaked only with acetone were utilized as controls. After drying the strips, 3-4 pairs of freshly moulted imagos of the cotton bug [Dysdercus cingulatus] were placed upon each strip. The development of the eggs which were laid daily by the imagos is as follows: 100 percent mortality of the eggs: No development of the embryos in the eggs laid on strips soaked with active substance.

Amount of Active active No. of No. of Mortality substance substance eggs larvae g/cm A 10" 151 100 B 10' 129 100 C 10' 354 3 99 D 10' 346 100 E 10 213 4 20 91 a F 10' 154 I 100 Control with acetone 251 240 4 Control without acetone 290 275 5 EXAMPLE l6 A disc of cotton material [10 cm'] was sprayed with an acetonic solution-of an active substance of this invention. An-untreated disc of material anda disc of material soaked only with acetone were utilized as controls. After drying the discs, 30-60 freshly laid eggs of the meal moth [Ephestia Kuhniella] were placed upon each disc. The disc was placed in a cage and held at 25C. and percent rel. humidity.

The development of eggs was registered over a few days. percent mortality of the eggs: No development of the embryos in the eggs laid on discs of material soaked with active substance.

Amount of Active active No. of No. of Mortality substance substance eggs larvae 10" g/cm A 10 20 100 10' 26 21 23 10' 46 36 22 B 10 76 100 10 35 1 97 10 50 39 22 C 10 65 100 10 29 21 28 10 25 17 32 D 10" 37 100 10 38 16 58 10 39 31 20 E 10 41 100 10 31 100 10 35 24 31 F 10 35 100 10" 35 10 71 10 34 22 35 G 10 40 100 10 31 23 26 l0 16 13 19 H 10' 62 100 10 47 44 6 10 78 75 4 l 10 98 100 10 49 28 43 10' 39 32 18 .1 10 49 3 94 10 31 26 16 10 28 25 11 Control with acetone 38 38 Control without acetone 42 39 7 We claim:

1. An insecticide composition, comprising an amount, effective for upsetting the hormonal balance of insects selected from the group consisting of Dysdercus cingulatus and Ephestia kuhniella, of a compound of the formula:

wherein R and R are methyl or ethyl, R is hydrogen or methyl, A and B are individually hydrogen or A and B taken together are a carbon to carbon bond or an oxygen bridge, X is oxygen or O-Cl-l and n is an integer of from 0 to 1; and an inert carrier.

2. The composition of claim 1 wherein said compound comprises between 0.01 and 0.5 percent of said composition.

3. The composition of claim 1 wherein said compound comprises 0.1 percent of said composition.

4. A method of controlling insects selected from the group consisting of Dysdercus cingulatus and Ephestia kuhniella, which comprises contacting said insects with an amount, effective for upsetting the hormonal balance of said insects, of a compound of the formula:

wherein R and R are methyl or ethyl, R is hydrogen or methyl, A and B are individually hydrogen or A and B taken together are a carbon to carbon bond or an oxygen bridge, X is oxygen or -OCH and n is an integer of from 0 to 1. 

2. The composition of claim 1 wherein said compound comprises between 0.01 and 0.5 percent of said composition.
 3. The composition of claim 1 wherein said compound comprises 0.1 percent of said composition.
 4. A method of controlling insects selected from the group consisting of Dysdercus cingulatus and Ephestia kuhniella, which comprises contacting said insects with an amount, effective for upsetting the hormonal balance of said insects, of a compound of the formula: 